Evidence map›Paper›PMID 32905676›Full record

Trial reportThe New England journal of medicine2020

Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide.

Karim Fizazi, Neal Shore, Teuvo L Tammela, Albertas Ulys, Egils Vjaters, Sergey Polyakov, Mindaugas Jievaltas, Murilo Luz, Boris Alekseev, Iris Kuss and 6 more

Registry-linked trialOpen access · bronzeAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in The New England journal of medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02200614 (A Multinational, Randomised, Double-blind, Placebo-controlled, Phase III Efficacy and Safety Study of Darolutamide), which is not on this map. Cited by 175 papers, 18 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
175citing papers in PubMed, 18 pooled it
29.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02200614 phase3completednot on this map

A Multinational, Randomised, Double-blind, Placebo-controlled, Phase III Efficacy and Safety Study of Darolutamide (ODM-201) in Men With High-risk Non-metastatic Castration-resistant Prostate Cancer

TypeinterventionalSponsorBayerRan2014 to 2021Enrolled1,509ConditionsProstate Cancer Non-Metastatic, Castration-ResistantArmsDarolutamide (Nubeqa, BAY1841788), Placebo
3 · Its place in the literature

Who cites it

175 citing papers in PubMed, 18 syntheses or guidelines pooled it, 348 citations in OpenAlex.

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115 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 13 institutions in 9 countries.

Karim FizaziFrom Institut Gustave Roussy, University of Paris-Saclay, Villejuif (K.F.), and Bayer Healthcare SAS, Loos (M.-A.L.B.) - both in France; Carolina Urologic Research Center, Myrtle Beach, SC (N.S.); Tampere University Hospital and Tampere University, Tampere (T.L.T.), and Orion Pharma, Espoo (A.S., T.S.) - both in Finland; the National Cancer Institute, Vilnius (A.U.), and the Lithuanian University of Health Sciences, Medical Academy, Kaunas (M.J.) - both in Lithuania; Stradins Clinical University Hospital, Riga, Latvia (E.V.); N.N. Alexandrov National Cancer Center of Belarus, Minsk, Belarus (S.P.); Hospital Erasto Gaertner, Curitiba, Brazil (M.L.); the National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow (B.A.); Clinical Statistics, Bayer, Berlin (I.K.); Bayer Healthcare, Whippany, NJ (O.P.); and the Massachusetts General Hospital Cancer Center, Boston (M.R.S.).
Neal ShoreFrom Institut Gustave Roussy, University of Paris-Saclay, Villejuif (K.F.), and Bayer Healthcare SAS, Loos (M.-A.L.B.) - both in France; Carolina Urologic Research Center, Myrtle Beach, SC (N.S.); Tampere University Hospital and Tampere University, Tampere (T.L.T.), and Orion Pharma, Espoo (A.S., T.S.) - both in Finland; the National Cancer Institute, Vilnius (A.U.), and the Lithuanian University of Health Sciences, Medical Academy, Kaunas (M.J.) - both in Lithuania; Stradins Clinical University Hospital, Riga, Latvia (E.V.); N.N. Alexandrov National Cancer Center of Belarus, Minsk, Belarus (S.P.); Hospital Erasto Gaertner, Curitiba, Brazil (M.L.); the National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow (B.A.); Clinical Statistics, Bayer, Berlin (I.K.); Bayer Healthcare, Whippany, NJ (O.P.); and the Massachusetts General Hospital Cancer Center, Boston (M.R.S.).
Teuvo L TammelaFrom Institut Gustave Roussy, University of Paris-Saclay, Villejuif (K.F.), and Bayer Healthcare SAS, Loos (M.-A.L.B.) - both in France; Carolina Urologic Research Center, Myrtle Beach, SC (N.S.); Tampere University Hospital and Tampere University, Tampere (T.L.T.), and Orion Pharma, Espoo (A.S., T.S.) - both in Finland; the National Cancer Institute, Vilnius (A.U.), and the Lithuanian University of Health Sciences, Medical Academy, Kaunas (M.J.) - both in Lithuania; Stradins Clinical University Hospital, Riga, Latvia (E.V.); N.N. Alexandrov National Cancer Center of Belarus, Minsk, Belarus (S.P.); Hospital Erasto Gaertner, Curitiba, Brazil (M.L.); the National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow (B.A.); Clinical Statistics, Bayer, Berlin (I.K.); Bayer Healthcare, Whippany, NJ (O.P.); and the Massachusetts General Hospital Cancer Center, Boston (M.R.S.).
Albertas UlysFrom Institut Gustave Roussy, University of Paris-Saclay, Villejuif (K.F.), and Bayer Healthcare SAS, Loos (M.-A.L.B.) - both in France; Carolina Urologic Research Center, Myrtle Beach, SC (N.S.); Tampere University Hospital and Tampere University, Tampere (T.L.T.), and Orion Pharma, Espoo (A.S., T.S.) - both in Finland; the National Cancer Institute, Vilnius (A.U.), and the Lithuanian University of Health Sciences, Medical Academy, Kaunas (M.J.) - both in Lithuania; Stradins Clinical University Hospital, Riga, Latvia (E.V.); N.N. Alexandrov National Cancer Center of Belarus, Minsk, Belarus (S.P.); Hospital Erasto Gaertner, Curitiba, Brazil (M.L.); the National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow (B.A.); Clinical Statistics, Bayer, Berlin (I.K.); Bayer Healthcare, Whippany, NJ (O.P.); and the Massachusetts General Hospital Cancer Center, Boston (M.R.S.).
Egils VjatersFrom Institut Gustave Roussy, University of Paris-Saclay, Villejuif (K.F.), and Bayer Healthcare SAS, Loos (M.-A.L.B.) - both in France; Carolina Urologic Research Center, Myrtle Beach, SC (N.S.); Tampere University Hospital and Tampere University, Tampere (T.L.T.), and Orion Pharma, Espoo (A.S., T.S.) - both in Finland; the National Cancer Institute, Vilnius (A.U.), and the Lithuanian University of Health Sciences, Medical Academy, Kaunas (M.J.) - both in Lithuania; Stradins Clinical University Hospital, Riga, Latvia (E.V.); N.N. Alexandrov National Cancer Center of Belarus, Minsk, Belarus (S.P.); Hospital Erasto Gaertner, Curitiba, Brazil (M.L.); the National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow (B.A.); Clinical Statistics, Bayer, Berlin (I.K.); Bayer Healthcare, Whippany, NJ (O.P.); and the Massachusetts General Hospital Cancer Center, Boston (M.R.S.).
Sergey PolyakovFrom Institut Gustave Roussy, University of Paris-Saclay, Villejuif (K.F.), and Bayer Healthcare SAS, Loos (M.-A.L.B.) - both in France; Carolina Urologic Research Center, Myrtle Beach, SC (N.S.); Tampere University Hospital and Tampere University, Tampere (T.L.T.), and Orion Pharma, Espoo (A.S., T.S.) - both in Finland; the National Cancer Institute, Vilnius (A.U.), and the Lithuanian University of Health Sciences, Medical Academy, Kaunas (M.J.) - both in Lithuania; Stradins Clinical University Hospital, Riga, Latvia (E.V.); N.N. Alexandrov National Cancer Center of Belarus, Minsk, Belarus (S.P.); Hospital Erasto Gaertner, Curitiba, Brazil (M.L.); the National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow (B.A.); Clinical Statistics, Bayer, Berlin (I.K.); Bayer Healthcare, Whippany, NJ (O.P.); and the Massachusetts General Hospital Cancer Center, Boston (M.R.S.).
Mindaugas JievaltasFrom Institut Gustave Roussy, University of Paris-Saclay, Villejuif (K.F.), and Bayer Healthcare SAS, Loos (M.-A.L.B.) - both in France; Carolina Urologic Research Center, Myrtle Beach, SC (N.S.); Tampere University Hospital and Tampere University, Tampere (T.L.T.), and Orion Pharma, Espoo (A.S., T.S.) - both in Finland; the National Cancer Institute, Vilnius (A.U.), and the Lithuanian University of Health Sciences, Medical Academy, Kaunas (M.J.) - both in Lithuania; Stradins Clinical University Hospital, Riga, Latvia (E.V.); N.N. Alexandrov National Cancer Center of Belarus, Minsk, Belarus (S.P.); Hospital Erasto Gaertner, Curitiba, Brazil (M.L.); the National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow (B.A.); Clinical Statistics, Bayer, Berlin (I.K.); Bayer Healthcare, Whippany, NJ (O.P.); and the Massachusetts General Hospital Cancer Center, Boston (M.R.S.).
Murilo LuzFrom Institut Gustave Roussy, University of Paris-Saclay, Villejuif (K.F.), and Bayer Healthcare SAS, Loos (M.-A.L.B.) - both in France; Carolina Urologic Research Center, Myrtle Beach, SC (N.S.); Tampere University Hospital and Tampere University, Tampere (T.L.T.), and Orion Pharma, Espoo (A.S., T.S.) - both in Finland; the National Cancer Institute, Vilnius (A.U.), and the Lithuanian University of Health Sciences, Medical Academy, Kaunas (M.J.) - both in Lithuania; Stradins Clinical University Hospital, Riga, Latvia (E.V.); N.N. Alexandrov National Cancer Center of Belarus, Minsk, Belarus (S.P.); Hospital Erasto Gaertner, Curitiba, Brazil (M.L.); the National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow (B.A.); Clinical Statistics, Bayer, Berlin (I.K.); Bayer Healthcare, Whippany, NJ (O.P.); and the Massachusetts General Hospital Cancer Center, Boston (M.R.S.).
Boris AlekseevFrom Institut Gustave Roussy, University of Paris-Saclay, Villejuif (K.F.), and Bayer Healthcare SAS, Loos (M.-A.L.B.) - both in France; Carolina Urologic Research Center, Myrtle Beach, SC (N.S.); Tampere University Hospital and Tampere University, Tampere (T.L.T.), and Orion Pharma, Espoo (A.S., T.S.) - both in Finland; the National Cancer Institute, Vilnius (A.U.), and the Lithuanian University of Health Sciences, Medical Academy, Kaunas (M.J.) - both in Lithuania; Stradins Clinical University Hospital, Riga, Latvia (E.V.); N.N. Alexandrov National Cancer Center of Belarus, Minsk, Belarus (S.P.); Hospital Erasto Gaertner, Curitiba, Brazil (M.L.); the National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow (B.A.); Clinical Statistics, Bayer, Berlin (I.K.); Bayer Healthcare, Whippany, NJ (O.P.); and the Massachusetts General Hospital Cancer Center, Boston (M.R.S.).
Iris KussFrom Institut Gustave Roussy, University of Paris-Saclay, Villejuif (K.F.), and Bayer Healthcare SAS, Loos (M.-A.L.B.) - both in France; Carolina Urologic Research Center, Myrtle Beach, SC (N.S.); Tampere University Hospital and Tampere University, Tampere (T.L.T.), and Orion Pharma, Espoo (A.S., T.S.) - both in Finland; the National Cancer Institute, Vilnius (A.U.), and the Lithuanian University of Health Sciences, Medical Academy, Kaunas (M.J.) - both in Lithuania; Stradins Clinical University Hospital, Riga, Latvia (E.V.); N.N. Alexandrov National Cancer Center of Belarus, Minsk, Belarus (S.P.); Hospital Erasto Gaertner, Curitiba, Brazil (M.L.); the National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow (B.A.); Clinical Statistics, Bayer, Berlin (I.K.); Bayer Healthcare, Whippany, NJ (O.P.); and the Massachusetts General Hospital Cancer Center, Boston (M.R.S.).
Marie-Aude Le BerreFrom Institut Gustave Roussy, University of Paris-Saclay, Villejuif (K.F.), and Bayer Healthcare SAS, Loos (M.-A.L.B.) - both in France; Carolina Urologic Research Center, Myrtle Beach, SC (N.S.); Tampere University Hospital and Tampere University, Tampere (T.L.T.), and Orion Pharma, Espoo (A.S., T.S.) - both in Finland; the National Cancer Institute, Vilnius (A.U.), and the Lithuanian University of Health Sciences, Medical Academy, Kaunas (M.J.) - both in Lithuania; Stradins Clinical University Hospital, Riga, Latvia (E.V.); N.N. Alexandrov National Cancer Center of Belarus, Minsk, Belarus (S.P.); Hospital Erasto Gaertner, Curitiba, Brazil (M.L.); the National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow (B.A.); Clinical Statistics, Bayer, Berlin (I.K.); Bayer Healthcare, Whippany, NJ (O.P.); and the Massachusetts General Hospital Cancer Center, Boston (M.R.S.).
Oana PetrenciucFrom Institut Gustave Roussy, University of Paris-Saclay, Villejuif (K.F.), and Bayer Healthcare SAS, Loos (M.-A.L.B.) - both in France; Carolina Urologic Research Center, Myrtle Beach, SC (N.S.); Tampere University Hospital and Tampere University, Tampere (T.L.T.), and Orion Pharma, Espoo (A.S., T.S.) - both in Finland; the National Cancer Institute, Vilnius (A.U.), and the Lithuanian University of Health Sciences, Medical Academy, Kaunas (M.J.) - both in Lithuania; Stradins Clinical University Hospital, Riga, Latvia (E.V.); N.N. Alexandrov National Cancer Center of Belarus, Minsk, Belarus (S.P.); Hospital Erasto Gaertner, Curitiba, Brazil (M.L.); the National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow (B.A.); Clinical Statistics, Bayer, Berlin (I.K.); Bayer Healthcare, Whippany, NJ (O.P.); and the Massachusetts General Hospital Cancer Center, Boston (M.R.S.).
Amir SnapirFrom Institut Gustave Roussy, University of Paris-Saclay, Villejuif (K.F.), and Bayer Healthcare SAS, Loos (M.-A.L.B.) - both in France; Carolina Urologic Research Center, Myrtle Beach, SC (N.S.); Tampere University Hospital and Tampere University, Tampere (T.L.T.), and Orion Pharma, Espoo (A.S., T.S.) - both in Finland; the National Cancer Institute, Vilnius (A.U.), and the Lithuanian University of Health Sciences, Medical Academy, Kaunas (M.J.) - both in Lithuania; Stradins Clinical University Hospital, Riga, Latvia (E.V.); N.N. Alexandrov National Cancer Center of Belarus, Minsk, Belarus (S.P.); Hospital Erasto Gaertner, Curitiba, Brazil (M.L.); the National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow (B.A.); Clinical Statistics, Bayer, Berlin (I.K.); Bayer Healthcare, Whippany, NJ (O.P.); and the Massachusetts General Hospital Cancer Center, Boston (M.R.S.).
Toni SarapohjaFrom Institut Gustave Roussy, University of Paris-Saclay, Villejuif (K.F.), and Bayer Healthcare SAS, Loos (M.-A.L.B.) - both in France; Carolina Urologic Research Center, Myrtle Beach, SC (N.S.); Tampere University Hospital and Tampere University, Tampere (T.L.T.), and Orion Pharma, Espoo (A.S., T.S.) - both in Finland; the National Cancer Institute, Vilnius (A.U.), and the Lithuanian University of Health Sciences, Medical Academy, Kaunas (M.J.) - both in Lithuania; Stradins Clinical University Hospital, Riga, Latvia (E.V.); N.N. Alexandrov National Cancer Center of Belarus, Minsk, Belarus (S.P.); Hospital Erasto Gaertner, Curitiba, Brazil (M.L.); the National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow (B.A.); Clinical Statistics, Bayer, Berlin (I.K.); Bayer Healthcare, Whippany, NJ (O.P.); and the Massachusetts General Hospital Cancer Center, Boston (M.R.S.).
Matthew R SmithFrom Institut Gustave Roussy, University of Paris-Saclay, Villejuif (K.F.), and Bayer Healthcare SAS, Loos (M.-A.L.B.) - both in France; Carolina Urologic Research Center, Myrtle Beach, SC (N.S.); Tampere University Hospital and Tampere University, Tampere (T.L.T.), and Orion Pharma, Espoo (A.S., T.S.) - both in Finland; the National Cancer Institute, Vilnius (A.U.), and the Lithuanian University of Health Sciences, Medical Academy, Kaunas (M.J.) - both in Lithuania; Stradins Clinical University Hospital, Riga, Latvia (E.V.); N.N. Alexandrov National Cancer Center of Belarus, Minsk, Belarus (S.P.); Hospital Erasto Gaertner, Curitiba, Brazil (M.L.); the National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow (B.A.); Clinical Statistics, Bayer, Berlin (I.K.); Bayer Healthcare, Whippany, NJ (O.P.); and the Massachusetts General Hospital Cancer Center, Boston (M.R.S.).
ARAMIS Investigators
Orion Corporation (Finland) · FIBayer (Germany) · DEBayer (United States) · USCarolina Urologic Research Center · USHospital Erasto Gaertner · BRLithuanian University of Health Sciences · LTMassachusetts General Hospital · USMinistry of Health of the Russian Federation · RUNational Cancer Institute · LTN.N. Alexandrov National Cancer Centre · BYPauls Stradiņš Clinical University Hospital · LVTampere University · FIUniversité Paris-Saclay · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDarolutamide is a structurally distinct androgen-receptor inhibitor that is approved for the treatment of nonmetastatic, castration-resistant prostate cancer. In the planned primary analysis of a phase 3 trial, the median metastasis-free survival was significantly longer with darolutamide (40.4 months) than with placebo (18.4 months). The data for the analysis of overall survival were immature at the time of the primary analysis.

methodsIn this double-blind, placebo-controlled trial, we randomly assigned 1509 men, in a 2:1 ratio, to receive darolutamide (955 patients) or placebo (554 patients) while they continued to receive androgen-deprivation therapy. After the results of the primary end-point analysis were found to be positive, unblinding of the treatment assignments occurred, and patients in the placebo group were permitted to cross over to receive open-label darolutamide treatment. At the time of this prespecified final analysis, which had been planned to be performed after approximately 240 deaths had occurred, overall survival and all other secondary end points were evaluated.

resultsThe median follow-up time was 29.0 months. At the time of unblinding of the data, all 170 patients who were still receiving placebo crossed over to receive darolutamide; 137 patients who had discontinued placebo before unblinding had occurred received at least one other life-prolonging therapy. Overall survival at 3 years was 83% (95% confidence interval [CI], 80 to 86) in the darolutamide group and 77% (95% CI, 72 to 81) in the placebo group. The risk of death was significantly lower, by 31%, in the darolutamide group than in the placebo group (hazard ratio for death, 0.69; 95% CI, 0.53 to 0.88; P = 0.003). Darolutamide was also associated with a significant benefit with respect to all other secondary end points, including the time to first symptomatic skeletal event and the time to first use of cytotoxic chemotherapy. The incidence of adverse events after the start of treatment was similar in the two groups; no new safety signals were observed.

conclusionsAmong men with nonmetastatic, castration-resistant prostate cancer, the percentage of patients who were alive at 3 years was significantly higher among those who received darolutamide than among those who received placebo. The incidence of adverse events was similar in the two groups. (Funded by Bayer HealthCare and Orion Pharma; ARAMIS ClinicalTrials.gov number, NCT02200614.).

Indexed as

AgedAndrogen Receptor AntagonistsCross-Over StudiesDouble-Blind MethodFatigueFractures, BoneHumansKaplan-Meier EstimateMaleMiddle AgedNeoplasm MetastasisProstate-Specific AntigenProstatic Neoplasms, Castration-ResistantPyrazolesAndrogen Receptor AntagonistsdarolutamideProstate-Specific AntigenPyrazoles

Identifiers

PMID32905676
OpenAlexW3084238852

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.